P-0297 Predictive/Prognostic Value of TS, KI-67, Egfr, MLH-1, MSH-2 and Trg in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiation (Bmg-B1-Study)

We previously reported that polyploid giant cancer cells (PGCCs) exhibit cancer stem cell properties and can generate daughter cells with the epithelial-mesenchymal transition phenotype. This study investigated the role of PGCC formation in the prognostic value of neoadjuvant chemoradiation therapy (nCRT) in locally advanced rectal cancer (LARC). The morphological characteristics were observed in patients with LARC after nCRT. Colorectal cancer cell lines were treated with irradiation or chemotherapeutic drugs, and the metastasis-related proteins were detected. 304 nCRT cases and 301 paired non-nCRT cases were collected for analysis. More PGCCs and morphologic characteristics related to invasion and metastasis appeared in tumor tissue after nCRT. Irradiation or chemicals could induce the formation of PGCCs with daughter cells exhibiting strong migratory, invasive, and proliferation abilities. In patients after nCRT, pathologic complete remission, partial remission, stable disease, and progressive disease were observed in 29 (9.54%), 125 (41.12%), 138 (45.39%), and 12 (3.95%) patients, respectively. Mucinous adenocarcinomas (MCs) occurred more frequently in nCRT than in non-nCRT patients (χ2 = 29.352, P=0.001), and the prognosis in MC patients was worse than that in non-MC patients (χ2 = 24.617, P=0.001). The difference in survival time had statistical significance for 60 days (χ2 = 5.357, P=0.021) and 70 days (χ2 = 18.830, P=0.001) rest interval time. On multivariable analysis, 60 days rest interval, Duke’s stage, and recurrence and/or distant metastasis remained significant predictors of survival. In conclusion, irradiation or chemicals induce the formation of PGCCs and PGCCs produce daughter cells with strong migration and invasion abilities after a long incubation period. Appropriate rest interval (incubation period) is very important for patients with LARC who will receive nCRT.

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The prognostic value of KRAS mutation in locally advanced rectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15090 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15090-e15090

Author(s):

Veli Bakalov ◽

Shaakir Hasan ◽

Stephen Abel ◽

Laila Babar ◽

Hira Shaikh ◽

...

Keyword(s):

Rectal Cancer ◽

Kras Mutation ◽

Prognostic Value ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Neoadjuvant Chemoradiation ◽

Multivariable Analyses ◽

Male Sex

e15090 Background: The prognostic value and prognostic value of the KRAS proto-oncogene mutation in colorectal cancer has been debated. Herein, we analyzed the National Cancer Database (NCDB) to assess the role of KRAS mutation as a prognostic marker in patients with locally advanced rectal cancer (LARC). Methods: We identified LARC patients treated with neoadjuvant chemoradiation from 2004-2015 excluding those with stage I/IV disease and unknown KRAS status.Multivariable logistic regression identified variables associated with KRAS positivity. Propensity adjusted univariable and multivariable analyses identified predictors of survival. Results: Of the 784 eligible patients, 506 and 278 were KRAS negative (KRAS-) and KRAS positive (KRAS+). Median survival was 63.6 months and 76.3 months for KRAS+ and KRAS-patients, with propensity adjusted 3 and 5-year survival of (79.9% vs. 83.6%) and (56.7% vs 61.9%) respectively (HR 1.56, p 1.074-2.272). Male sex, no insurance, and KRAS+ disease was associated with poorer survival on unadjusted and propensity adjusted multivariable analyses (Table). Conclusions: Our analysis of KRAS+ LARC suggest that KRAS+ disease is associated with poorer overall survival. Given the inherent limitations of retrospective data, prospective validation is warranted. [Table: see text]

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Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001610 ◽

2021 ◽

Vol 9 (3) ◽

pp. e001610

Author(s):

Incheol Seo ◽

Hye Won Lee ◽

Sang Jun Byun ◽

Jee Young Park ◽

Hyeonji Min ◽

...

Keyword(s):

Rectal Cancer ◽

Locally Advanced ◽

Enrichment Analysis ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Neoadjuvant Chemoradiation ◽

Cytolytic Activity ◽

Gene Set Enrichment Analysis ◽

Preoperative Treatment ◽

Rna Seq

BackgroundNeoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.MethodsWe analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.ResultsGene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.ConclusionsTaken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

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